Medical 'superglue' shows promise for heart surgery

“A medical superglue has been developed that has the potential to patch heart defects on the operating table,” BBC News reports.

The glue has currently only be used in animals, but the results are encouraging.

Medical glue is currently used to close minor skin wounds in some operations, but its use has been limited for several reasons – it can be activated by contact with blood before it reaches its intended position, for example, and is also water soluble, so it can be washed away.

This study used a newly developed type of glue that is thick and sticky until it is activated by ultraviolet (UV) light. In the experiments, it was used to:

attach a patch to the septum (the part separating the left and right chambers of the heart) of pigs’ hearts while they were still beating

apply a patch to a hole in the hearts of several rats

repair a small cut in a pig’s artery and withstand pressures higher than normal blood pressure

On the whole, these experiments were successful, but the animals were only monitored for a short period of time after surgery.

This research has great potential for the future, but longer term studies are required to assess for complications or any toxic effects before human experiments will be possible.

If experiments prove successful, this superglue could revolutionise surgery for cases where surgeons need to repair the damage resulting from a heart attack, or in the treatment of children born with a defective heart (congenital heart disease).

Where did the story come from?

The study was carried out by researchers from Boston Children’s Hospital, Harvard Medical School, Brigham and Women’s Hospital and the Massachusetts Institute of Technology in the US, the University of Coimbra in Portugal, and the Department of Pediatric Cardiology in Bolivia.

It was funded by the Center for Integration of Medicine and Innovative Technology, Boston Children’s hospital and the National Institutes of Health in the US, the Portuguese Foundation for Science and Technology, and the German Research Foundation.

It was published in the peer-reviewed medical journal Science Translational Medicine.

The study was accurately reported by BBC News.

What kind of research was this?

This was a laboratory study investigating a new technology carried out in animals. The researchers aimed to create a type of glue that would be strong enough to attach tissues or other materials together during surgery on areas of high blood flow.

Usually, during surgery tissues are held together with stitches or staples, but this can cause damage to the tissues, is time consuming and does not make a watertight seal.

Existing medical glues are not strong enough to use in challenging situations, for example where there is high blood flow or if the tissue is moving (contracting), such as in the heart.

There have also been other limitations, such as the glue being activated by contact with blood before it reaches the intended position, medics not being able to reposition the glue, and the fact that the glue is water soluble and can therefore be washed away. A further limitation of the glue being water soluble is that it can swell up and tear.

The researchers were inspired by the ability of slugs and sandcastle worms, a type of worm found in California known to produce a strong “underwater” glue. These creatures can produce viscous (thick and sticky) secretions that are not easily washed away and do not mix with water.

They wanted to develop a glue that would imitate natural substances, be stable, not dissolve in water, be activated by light once in the right place, and be able to achieve a flexible watertight bond.

What did the research involve?

A compound (mixture) of two naturally occurring substances – glycerol and sebacic acid – was developed, which the researchers dubbed hydrophobic (insoluble) light-activated adhesive (HLAA). The mixture is very viscous and easy to spread over a surface. When activated by ultraviolet (UV) light, it becomes a strong, flexible adhesive.

To get the strongest glue, the researchers experimented with:

different amounts of glycerol and sebacic acid

light intensity

length of time the light was used

HLAA was used in operations on small and large animals that would be similar to human operations, including the repair of cuts to blood vessels and closing holes in the wall of the heart.

Researchers performed a series of experiments:

they compared patches covered in HLAA with current medical glue by sticking them to the outside of rats’ hearts

they compared HLAA to conventional stitches by making a hole in the heart of two groups of rats, and used the HLAA patches to close it in one group (n=19) and compared this to using stitches in the other (n=15)

they put patches coated with HLAA on the septum of four pigs’ hearts

they glued a small cut measuring 3-4mm to a pig artery in the laboratory using HLAA and then assessed at what pressures it would remain closed to see if it could cope with human blood pressures

What were the basic results?

The research found that HLAA was 50% as strong as the medical glue currently in use. However, when the researchers put the glue onto patches, they were able to put it into position without the glue being washed off. They were then able to fix it with UV light.

When the same technique was performed using the current type of glue, it was immediately activated when it came into contact with the blood and was therefore harder to use.

Patches covered with HLAA were stuck to the outer layer of the hearts of rats and could be repositioned before sticking with the UV light, whereas the patches using current medical glue could not. After seven days, all of the patches were attached in both groups (n=3).

The researchers performed the same operation and monitored the rats for 14 days (HLAA n=5 and current medical glue n=4). The degree of tissue death and inflammation was significantly less in the HLAA group. There was no difference between the groups for heart function.

For the heart wall defects, successful closure was achieved with HLAA patches in 17 of the 19 rats, but one died from bleeding complications four days later. The 6mm diameter patch did not cover the 2mm hole in three of the rats.

As the researchers point out, rats’ hearts beat six to seven times faster than human hearts, so they do not think this would be as difficult to achieve in humans.

Successful closure with stitches was achieved in 14 out of 15 rats. There was no significant difference between the groups after 28 days, although all had reduced heart function in the area of the repair.

The patch to the pigs’ septum stayed in place until the pigs were put down 4 or 24 hours after the surgery.

Applying the glue without a patch to cuts of 3-4mm in pig arteries created a seal that was able to stay together withstanding pressures of up to 203.5mmHg, ± 28.5mmHg.

This is impressive, as the systolic pressure (the level of blood pressure as the heart beats out) of human arteries is usually around 120mmHg.

How did the researchers interpret the results?

The researchers reported that the HLAA “achieves a strong level of adhesion to wet tissue and is not compromised by pre-exposure to blood … it could be used for many cardiovascular and surgical applications”.

They also acknowledge that, “For translation into humans, additional safety and toxicity studies may be required”.

Conclusion

This innovative glue has shown promise during animal experiments involving rats and pigs. The consistency and technique of “fixing” the glue appears to show some advantages for new surgical techniques, but there are some limitations that need to be addressed before it can be tested in humans.

The researchers mention that the “rapid curing” (the light treatment process) helped avoid exposure to high temperatures, but it is not clear what effect the UV light may have on surrounding tissues. The animals were also only followed up for a short period of time after the surgery. It would be important to find out if there are any longer term side effects of using this technique.

This research has great potential for the future, but longer term studies will be required to assess for complications and any toxic effects before human experiments will be possible.

An operation that targets the nerves connected to the kidney has been found to significantly reduce blood pressure in patients with hypertension, according to a clinical trial involving UK researchers.

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